This study concerns the development of methods for prenatal diagnosis of the hemoglobinopathies and the delineation of the molecular lesion in the thalassemias. For prenatal diagnosis, we are expanding our search for restriction endonuclease polymorphisms which will be used for linkage analysis of the globin gene. In thalassemia, we plan to study the molecular defect which allows for the non-deletion type of a thalassemia by isolating the gene by cloning and performing structural and functional analysis. In beta thalassemia, we will search for additional nonsense mutations at the codons.